Laos fever

Laos fever is an acute zoonotic natural focal viral disease from the group of especially dangerous viral infections in Africa. It is characterized by the phenomena of universal capillary toxicosis, damage to the liver, kidneys, central nervous system, and high mortality. Symptoms of Laos fever: fever, hemorrhagic syndrome, development of renal failure.

The first five cases of the disease were registered and described in the town of Lassa (Nigeria) in 1969 by nurses and researchers (three cases were fatal). The pathogen was isolated in 1970. Currently, Lassa fever is widespread in the countries of West and Central Africa (Sierra Leone, Nigeria, Liberia, Guinea, Senegal, Mali, Central African Republic, Burkina Faso). Imported cases of infection have been registered in the USA, Europe, Israel, and Japan.

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Epidemiology of Laos fever

The reservoir and source of infection are African rats of the genus Mastomys (M. natalensis, M. huberti, M. erythroleucus), the infection rate of which in epidemic foci can reach 15-17%. Infection in rodents can be lifelong in the form of chronic asymptomatic persistence of the virus, excreted with saliva, feces and urine. Sources of infection also include sick people, whose contagiousness remains throughout the entire period of the disease; in this case, all human excreta can be infectious.

The mechanism of transmission of Laos fever is varied. In rodents, the virus is transmitted by drinking and eating food contaminated with the urine of virus-carrying rats, as well as vertically. Infection of people in natural foci and at home is possible by drinking water and food contaminated with rat urine, by contact-household means through household items, by stripping the skins of killed animals. The ability of the virus to penetrate the human body through the respiratory system, damaged skin, mucous membranes, and the gastrointestinal tract causes the transmission of infection in various ways - airborne, alimentary, contact, sexual, vertical.

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Natural susceptibility of people

Lassa fever is a disease with a moderate level of contagiousness, but a high mortality rate (from 18 to 60%). In most endemic areas of Africa, it is registered all year round, with some increase in incidence in January-February (the period of rodent migration to human habitation). Immunity has been little studied, but specific antibodies persist in those who have recovered for 5-7 years.

Main epidemiological features of Laos fever

The highest incidence is observed among the population living in West Africa. The disease is endemic in both rural and urban areas, which is explained by the high population density of rodents of the genus Mastomys. Secondary cases of the disease (infection from one patient) are often observed, but further chain transmission of the virus is also possible. Imported cases of infection have been registered in New York, Hamburg, Japan, and Great Britain.

Healthcare workers are a special risk group. Infection can occur through various biological secretions of the patient, medical instruments contaminated with blood, and also through the air from patients who release large portions of the virus when coughing. Intrahospital outbreaks of Lassa fever are known in Liberia, Nigeria and other countries.

Causes of Laos Fever

Laos fever is caused by arenaviruses, which belong to the family of RNA-containing non-enveloped viruses. The family Arenaviridae got its name from the Greek arenosa - sandy (due to the presence of ribosomes in the virion, similar to grains of sand). The family includes the lymphocytic choriomeningitis virus, as well as the Lassa, Junin, Machupo, and Guanarito viruses, which cause severe hemorrhagic fevers.

Characteristics of hemorrhagic fevers of the Arenaviridae family

Name of the virus	Name of the disease	Spreading	Natural reservoir
Lassa	Lassa fever	West Africa (especially Sierra Leone, Guinea, Nigeria)	Mastomys huberti, Mastomys erythroleucus Mastomys, natalensis
Junin	Argentine GL	Argentina	Calomys Musculinis
Machupo	Bolivian GL	Bolivia	Calomys callosus
Guanarito	Venezuelan GL	Venezuela	Zygodontomys brevicauda
Sabia	Brazilian GL	Brazil	Unknown

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Structure and reproduction

The virion is spherical or oval in shape and about 120 nm in diameter. It is surrounded by a membrane with club-shaped glycoprotein spikes GP1 and GP2. Under the membrane are 12-15 cellular ribosomes, similar to grains of sand. The capsid has a spiral shape. The genome is represented by two segments (L, S) of single-stranded minus RNA; it encodes 5 proteins, in particular L-, Z-, N-, G-proteins. The virion contains transcriptase (L-protein, RNA polymerase). Reproduction occurs in the cytoplasm; after assembly and inclusion of ribosome-like particles into the virion, it buds through the plasma membrane of the cell.

Resistance

Arenaviruses are sensitive to the action of detergents, UV and gamma radiation, and heating, and are insensitive to freezing and lyophilization.

Cultivation

Arenaviruses are cultured in chicken embryos, in rodents, and in cell cultures, such as green monkey kidney cell cultures.

In recent years, several more viruses belonging to this family (Mopeia, Mobala, Ippy, Amapari, Flexal, Cupixni, Tamiami, Bear Canyon) have been identified in Africa, South and North America, but their role in human pathology has not yet been established. According to experts, a new virus of this family is discovered every three years.

Humans have a high natural susceptibility to arenaviruses, and immunity is strong and long-lasting.

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Pathogenesis of Laos fever

Laos fever has not been studied sufficiently. Rodents and monkeys of various species are used as models for studying the mechanisms of infection development.

The entry points for the virus are most often the mucous membranes of the respiratory and gastrointestinal tracts. During the incubation period, the pathogen actively multiplies in the regional lymph nodes, after which persistent and severe viremia develops with dissemination of the virus throughout the organs of the mononuclear-phagocytic system. An important pathogenetic role of the MPS in the development of the disease has been established. When monocytes are affected by the virus, a significant release of cytokines (TNF, IL-1.6, etc.) occurs; the latter are associated with the occurrence of multiple organ pathology, impaired vascular permeability (endothelial damage), the development of DIC syndrome, infectious toxic shock, and collapse. Cells of vital organs infected with the virus become a target for cytotoxic T-lymphocytes. As a result of the formation of immune complexes and their fixation on the basal membranes of cells, severe necrotic processes develop in the liver, spleen, kidneys, adrenal glands, and myocardium. Inflammatory phenomena are weakly expressed, and changes in the brain are not detected.

The delayed nature of the production of virus-neutralizing antibodies and disturbances of cellular immune responses in the acute febrile period of the disease are presumably the cause of the development of a severe infectious process with an early fatal outcome. During autopsy of deceased patients, significant blood filling in the spleen, liver, and red bone marrow is noticeable.

Symptoms of Laos Fever

The incubation period for Laos fever is usually 7-12 days, with possible variations from 3 to 16 days.

Most cases of Lassa fever occur in a latent or subclinical form.

In moderate cases, Laos fever often begins gradually with low fever, malaise, myalgia, sore throat when swallowing, conjunctivitis. After a few days, typical symptoms of Laos fever are noted: body temperature (with chills) rises to 39-40 °C, headache, weakness increase, apathy develops. 60-75% of patients note significant pain in the retrosternal and lumbar regions, in the back, chest, and somewhat less often in the abdomen. Cough, nausea, and vomiting often occur (in 50-60% of cases). Diarrhea (sometimes in the form of melena), dysuria, and convulsions are possible. Some patients develop visual impairment. When examining patients, attention is drawn to hyperemia of the face, neck and chest skin, sometimes facial edema, manifestations of hemorrhagic syndrome of various localizations, exanthema of a petechial, maculopapular or erythematous nature, peripheral lymphadenopathy. Tonsillitis also develops (in 60% of cases), less often - ulcerative pharyngitis: white spots appear on the mucous membrane of the pharynx, soft palate, arches, tonsils, later turning into ulcers with a yellow bottom and a red rim, often localized on the arches. Heart sounds are significantly muffled, bradycardia and arterial hypotension are noted. The acute febrile period can last up to 3 weeks, the temperature decreases lytically. Recovery is very slow, relapses of the disease are possible.

Severe course (35-50% of cases) is characterized by symptoms of multiple organ damage - liver, lungs (pneumonia), heart (myocarditis), etc. CNS damage can manifest itself in the development of encephalopathy, encephalitis, meningitis (serous). The disease is especially severe in children under 2 years old, with frequent development of hemorrhagic syndrome, bleeding. The following clinical signs are prognostically unfavorable: hypotension (shock, collapse), severe hemorrhagic syndrome (bleeding), oligo- and anauria, facial edema, development of pulmonary edema, ascites, myocarditis, significant increase in ALT, high level of viremia determined by PCR. With an unfavorable course of the disease, fatal outcomes are often observed at the beginning of the second week of the disease.

Complications of Laos fever

Laos fever may be complicated by infectious toxic shock, pneumonia, myocarditis, acute renal failure, delirium. In the 2nd-3rd week of the disease, pericarditis, uveitis, orchitis, as well as complications associated with damage to the cranial nerves (most often the 8th pair - deafness) are possible. In severe forms of the disease, the mortality rate is 30-50%. The mortality rate of hospitalized patients is from 15 to 25%.

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Diagnosis of Laos fever

Differential diagnosis of Laos fever is difficult, especially in the early phase of Lassa fever development. When making a preliminary diagnosis, great clinical significance is given to the combination of fever, retrosternal pain, ulcerative pharyngitis, proteinuria. This combination of symptoms is observed in 70% of patients and allows clinical suspicion of the disease.

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Laboratory diagnostics of Laos fever

Characteristic changes in the hemogram: leukopenia, and later - leukocytosis and a sharp increase in ESR (up to 40-80 mm per hour), a decrease in blood clotting time, an increase in prothrombin time. Characteristic changes in urine - proteinuria, cylindruria, an increase in the number of leukocytes and erythrocytes.

From the first days of the disease, the virus can be isolated from pharyngeal washes, blood and urine. ELISA (detection of the virus antigen or determination of IgM antibodies) is used as a method of express diagnostics. Subsequently, RNGA and RSK are used to determine antiviral antibodies. According to WHO recommendations, a preliminary diagnosis of Lassa fever is made in febrile patients in endemic areas in the presence of IgG antibodies in titers of 1:512 or higher and simultaneous detection of IgM. A PCR diagnostic method has also been developed.

Laos fever treatment

Hospitalization of patients in specialized infectious disease departments with strict isolation and bed rest is mandatory. Pathogenetic treatment of Laos fever is aimed at correcting metabolic disorders (metabolic acidosis), restoring circulating blood volume, and stopping hemorrhagic syndrome. Symptomatic agents are prescribed; antibiotics and glucocorticosteroids can be used if complications develop. The effectiveness of convalescent plasma is questionable: a positive effect is observed only in some cases when prescribed in the first week of the disease, and when administered at a later date, the patient's condition may worsen. The use of ribavirin in the early phase (up to the 7th day of illness) can reduce the severity of the disease and reduce mortality to 5%. The drug is administered orally at 1000 mg / day for 10 days or intravenously. For intravenous administration, the initial dose is 30 mg/kg body weight, then ribavirin is administered at 15 mg/kg body weight every 6 hours for 4 days, and in the following 6 days - at 7.5 mg/kg body weight every 8 hours. Etiotropic agents and vaccines are being developed.

How is Laos fever prevented?

Prevention of Laos fever is limited to preventing rats, sources of infection, from entering homes, protecting food and household items from contamination by rodent excrement or dust. Medical personnel should be trained in the rules of working with highly contagious patients and in following a strict anti-epidemic regime. Lassa fever is prevented by using ribavirin 500 mg orally every 6 hours for 7 days. Specific prevention has not been developed.